Paired nasopharyngeal and deep lung testing for SARS-CoV2 reveals a viral gradient in critically ill patients: a multi-centre study

Introduction Samples for diagnostic tests for SARS-CoV-2 can be obtained from the upper (nasopharyngeal/oropharyngeal swabs) or lower respiratory tract (sputum or tracheal aspirate or broncho-alveolar lavage - BAL). Data from different testing sites indicates different rates of positivity. Reverse-transcriptase polymerase chain reaction (RT-PCR) allows for semi-quantitative estimates of viral load as time to crossing threshold (Ct) is inversely related to viral load. Objectives The objective of our study was to evaluate SARS-CoV2 RNA loads between paired nasopharyngeal (NP) and deep lung (endotracheal aspirate or BAL) samples from critically ill patients. Methods SARS-CoV-2 RT-PCR results were retrospectively reviewed for 51 critically ill patients from 5 intensive care units in 3 hospitals ; Addenbrookes Hospital Cambridge (3 units), Royal Papworth Cambridge (1 unit), and Royal Sunderland Hospital (1 unit). At the times when paired NP and deep lung samples were obtained, one patient had been on oxygen only, 6 patients on non-invasive ventilation, 18 patients on ECMO, and 26 patients mechanically ventilated. Results Results collected showed significant gradient between NP and deep lung viral loads. Median Ct value was 29 for NP samples and 24 for deep lung samples. Of 51 paired samples, 16 were negative (below limit of detection) on NP swabs but positive (above limit of detection) on deep lung sample, whilst 2 were negative on deep sample but positive on NP (both patients were on ECMO). Conclusions It has been suggested that whilst SARS-CoV1 tends to replicate in the lower respiratory tract, SARS-CoV2 replicates more vigorously in the upper respiratory tract. These data challenge that assumption. These data suggest that viral migration to, and proliferation in, the lower respiratory tract may be a key factor in the progression to critical illness and the development of severe acute respiratory syndrome (SARS). Factors which promote this migration should be examined for association with severe COVID-19. From a practical point of view, patients with suspected severe COVID-19 should have virological samples obtained from the lower respiratory tract where-ever possible, as upper respiratory samples have a significant negative rate.

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Relationship Between Upper Respiratory Tract Influenza Test Result and Clinical Outcomes Among Critically Ill Influenza Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofw023 ◽

2016 ◽

Vol 3 (1) ◽

Cited By ~ 10

Author(s):

Krishna P. Reddy ◽

Ednan K. Bajwa ◽

Robert A. Parker ◽

Andrew B. Onderdonk ◽

Rochelle P. Walensky

Keyword(s):

Respiratory Tract ◽

Disease Progression ◽

Clinical Outcomes ◽

Critically Ill ◽

Critically Ill Patients ◽

Lower Respiratory Tract ◽

Diagnostic Yield ◽

Upper Respiratory Tract ◽

Upper Respiratory ◽

Test Result

Abstract Among critically ill patients with lower respiratory tract (LRT)-confirmed influenza, we retrospectively observed worse 28-day clinical outcomes in upper respiratory tract (URT)-negative versus URT-positive subjects. This finding may reflect disease progression and highlights the need for influenza testing of both URT and LRT specimens to improve diagnostic yield and possibly inform prognosis.

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Viral load in upper respiratory tract of COVID-19 patients detected by digital PCR

10.21203/rs.3.rs-29834/v1 ◽

2020 ◽

Cited By ~ 1

Author(s):

Jiankang Zhao ◽

Haibo Li ◽

Hui Li ◽

Qiaoling Wu ◽

Ke Wu ◽

...

Keyword(s):

Viral Load ◽

Respiratory Tract ◽

Digital Pcr ◽

Upper Respiratory Tract ◽

Rt Pcr ◽

Lung Lesions ◽

Viral Loads ◽

Ct Value ◽

Upper Respiratory ◽

Close Contacts

Abstract Background: Upper respiratory tract specimens are widely applicable for the diagnosis of COVID-19. To date, no study has analyzed the actual viral loads in upper respiratory tract and its relationship with the severity of lung lesions, Ct value of RT-PCR and transmission capacity in COVID-19 patients.Methods: We retrospectively enrolled nine COVID-19 patients. Clinical data and close contacts of these patients were investigated. Respiratory samples were tested for SARS-CoV-2 with both normal RT-PCR and droplet digital PCR.Results: All the COVID-19 patients complicated with pneumonia. Viral loads in nasopharyngeal swabs were accurately quantified, and they had no direct correspondence with the severity of lung lesions. The Cycle Threshold (Ct) value of RT-PCR was approximately consistent with the absolute quantification of digital PCR. The spearman correlation coefficient between them was -0.952 with P value < 0.001. Close contacts of patients with very low viral load or no detected virus were not infected.Conclusions: Viral loads in nasopharyngeal swabs, could not predict the severity of lung lesions revealed by CT in COVID-19 patients. The infectious capacity of patients with low or absent viral load in upper respiratory tract was relatively weak, and wearing mask might be helpful for lower its spread.

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Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020

Eurosurveillance ◽

10.2807/1560-7917.es.2020.25.32.2001483 ◽

2020 ◽

Vol 25 (32) ◽

Cited By ~ 43

Author(s):

Anika Singanayagam ◽

Monika Patel ◽

Andre Charlett ◽

Jamie Lopez Bernal ◽

Vanessa Saliba ◽

...

Keyword(s):

Viral Load ◽

Severe Acute Respiratory Syndrome ◽

Respiratory Tract ◽

Symptom Onset ◽

Infectious Virus ◽

Upper Respiratory Tract ◽

Threshold Values ◽

Rt Pcr ◽

Cycle Threshold ◽

Upper Respiratory

Severe acute respiratory syndrome coronavirus 2 viral load in the upper respiratory tract peaks around symptom onset and infectious virus persists for 10 days in mild-to-moderate coronavirus disease (n = 324 samples analysed). RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset; it is similar in asymptomatic and symptomatic persons. Asymptomatic persons represent a source of transmissible virus.

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Prevalence and clinical course of upper airway respiratory virus infection in critically ill patients with hematologic malignancies

PLoS ONE ◽

10.1371/journal.pone.0260741 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0260741

Author(s):

Jongmin Lee ◽

Seok Chan Kim ◽

Chin Kook Rhee ◽

Jaewoong Lee ◽

Jong Wook Lee ◽

...

Keyword(s):

Respiratory Tract ◽

Critically Ill ◽

Critically Ill Patients ◽

Respiratory Virus ◽

Upper Airway ◽

Hematologic Malignancies ◽

High Dose ◽

Upper Respiratory Tract ◽

Anti Cancer ◽

Upper Respiratory

Background The clinical significance of upper airway respiratory virus (RV) detection in patients with hematologic malignancies remains unclear. We aimed to investigate the association between upper airway RV detection and prognosis in critically ill patients with hematologic malignancies. Methods This retrospective observational study included 331 critically ill patients with hematologic malignancies who presented respiratory symptoms and their nasopharyngeal swab was tested using a multiplex PCR assay between January 2017 and December 2018. A logistic regression model was used to adjust for potential confounding factors in the association between assay positivity and in-hospital mortality. Results Among the 331 analyzed patients, RVs were detected in 29.0%. The overall mortality rates in the intensive care unit and hospital were 56.8% and 65.9%, respectively. Positive upper airway RV detection was associated with relapsed hematologic malignancies, higher level of C-reactive protein, and prior use of high dose steroids and anti-cancer chemotherapeutic drugs. Furthermore, it was independently associated with in-hospital mortality (adjusted odds ratio, 2.36; 95% confidence interval, 1.23 to 4.54). Among different RVs, parainfluenza virus was more prevalent among patients who died in the hospital than among those who survived (11.5% vs. 3.5%, P = 0.027). Conclusions RV detection in the upper respiratory tract was relatively common in our cohort and was significantly associated with a poor prognosis. Thus, it can be used as a predictor of prognosis. Moreover, RV presence in the upper respiratory tract should be examined in patients who have previously been prescribed with high dose corticosteroids and anti-cancer drugs.

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Enhanced severity of virus associated lower respiratory tract disease in asthma patients may not be associated with delayed viral clearance and increased viral load in the upper respiratory tract

Journal of Clinical Virology ◽

10.1016/j.jcv.2007.10.028 ◽

2008 ◽

Vol 41 (2) ◽

pp. 116-121 ◽

Cited By ~ 33

Author(s):

Leontine J.R. van Elden ◽

Alfred P.E. Sachs ◽

Anton M. van Loon ◽

Monique Haarman ◽

David A. van de Vijver ◽

...

Keyword(s):

Viral Load ◽

Respiratory Tract ◽

Lower Respiratory Tract ◽

Viral Clearance ◽

Upper Respiratory Tract ◽

Respiratory Tract Disease ◽

Lower Respiratory Tract Disease ◽

Asthma Patients ◽

Upper Respiratory ◽

Tract Disease

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Prevalence and Clinical Course of Upper Airway Respiratory Virus Infection in Critically Ill Patients with Hematologic Malignancies

10.21203/rs.3.rs-31868/v1 ◽

2020 ◽

Author(s):

Jongmin Lee ◽

Seok Chan Kim ◽

Chin Kook Rhee ◽

Jaewoong Lee ◽

Jong Wook Lee ◽

...

Keyword(s):

Respiratory Tract ◽

Critically Ill ◽

Critically Ill Patients ◽

Respiratory Virus ◽

Upper Airway ◽

Hematologic Malignancies ◽

High Dose ◽

Upper Respiratory Tract ◽

Anti Cancer ◽

Upper Respiratory

Abstract Background The clinical significance of upper airway respiratory virus (RV) detection in patients with hematologic malignancies remains unclear. We aimed to investigate the association between upper airway RV detection and prognosis in critically ill patients with hematologic malignancies. Methods This retrospective observational study included 331 critically ill patients with hematologic malignancies who presented respiratory symptoms and their nasopharyngeal swab was tested using a multiplex PCR assay between January 2017 and December 2018. A logistic regression model was used to adjust for potential confounding factors in the association between assay positivity and in-hospital mortality. Results Among the 331 analyzed patients, RVs were detected in 29.0%. The overall mortality rates in the intensive care unit and hospital were 56.8% and 65.9%, respectively. Positive upper airway RV detection was associated with relapsed hematologic malignancies, higher level of C-reactive protein, and prior use of high dose steroids and anti-cancer chemotherapeutic drugs. Furthermore, it was independently associated with in-hospital mortality (adjusted odds ratio, 2.36; 95% confidence interval, 1.23 to 4.54). Among different RVs, parainfluenza virus was more prevalent among patients who died in the hospital than among those who survived (11.5% vs. 3.5%, P = 0.027). Conclusions RV detection in the upper respiratory tract was relatively common in our cohort and was significantly associated with a poor prognosis. Thus, it can be used as a predictor of prognosis. Moreover, RV presence in the upper respiratory tract should be examined in patients who have previously been prescribed with high dose corticosteroids and anti-cancer drugs.

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SARS-CoV-2 detection in the lower respiratory tract of invasively ventilated ARDS patients

Critical Care ◽

10.1186/s13054-020-03323-5 ◽

2020 ◽

Vol 24 (1) ◽

Author(s):

Niccolò Buetti ◽

Paul-Henri Wicky ◽

Quentin Le Hingrat ◽

Stéphane Ruckly ◽

Timothy Mazzuchelli ◽

...

Keyword(s):

Viral Load ◽

Respiratory Tract ◽

Critically Ill ◽

Critically Ill Patients ◽

Lower Respiratory Tract ◽

Logistic Models ◽

Time Interval ◽

Mixed Effect ◽

Viral Shedding ◽

Binational Study

Abstract Background Data on SARS-CoV-2 load in lower respiratory tract (LRT) are scarce. Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients. Methods We conducted a binational study merging prospectively collected data from two COVID-19 reference centers in France and Switzerland. First, we described the viral shedding duration (i.e., time to negativity) in LRT samples. Second, we analyzed viral load in LRT samples. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms’ onset and date of sampling. Results From March to May 2020, 267 LRT samples were performed in 90 patients from both centers. The median time to negativity was 29 (IQR 23; 34) days. Prolonged viral shedding was not associated with age, gender, cardiac comorbidities, diabetes, immunosuppression, corticosteroids use, or antiviral therapy. The LRT viral load tended to be higher in non-survivors. This difference was statistically significant after adjusting for the time interval between onset of symptoms and date of sampling (OR 3.78, 95% CI 1.13–12.64, p = 0.03). Conclusions The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the viral load in the LRT was associated with the 6-week mortality.

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The lower respiratory tract microbiome of critically ill patients with COVID-19

Scientific Reports ◽

10.1038/s41598-021-89516-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Paolo Gaibani ◽

Elisa Viciani ◽

Michele Bartoletti ◽

Russell E. Lewis ◽

Tommaso Tonetti ◽

...

Keyword(s):

Respiratory Tract ◽

Critically Ill ◽

Critically Ill Patients ◽

Lower Respiratory Tract ◽

Multidrug Resistant ◽

Carbapenem Resistant ◽

Lung Microbiome ◽

Bacterial Microbiome ◽

Unweighted Unifrac ◽

Bacterial Superinfection

AbstractCOVID-19 infection may predispose to secondary bacterial infection which is associated with poor clinical outcome especially among critically ill patients. We aimed to characterize the lower respiratory tract bacterial microbiome of COVID-19 critically ill patients in comparison to COVID-19-negative patients. We performed a 16S rRNA profiling on bronchoalveolar lavage (BAL) samples collected between April and May 2020 from 24 COVID-19 critically ill subjects and 24 patients with non-COVID-19 pneumonia. Lung microbiome of critically ill patients with COVID-19 was characterized by a different bacterial diversity (PERMANOVA on weighted and unweighted UniFrac Pr(> F) = 0.001) compared to COVID-19-negative patients with pneumonia. Pseudomonas alcaligenes, Clostridium hiranonis, Acinetobacter schindleri, Sphingobacterium spp., Acinetobacter spp. and Enterobacteriaceae, characterized lung microbiome of COVID-19 critically ill patients (LDA score > 2), while COVID-19-negative patients showed a higher abundance of lung commensal bacteria (Haemophilus influenzae, Veillonella dispar, Granulicatella spp., Porphyromonas spp., and Streptococcus spp.). The incidence rate (IR) of infections during COVID-19 pandemic showed a significant increase of carbapenem-resistant Acinetobacter baumannii (CR-Ab) infection. In conclusion, SARS-CoV-2 infection and antibiotic pressure may predispose critically ill patients to bacterial superinfection due to opportunistic multidrug resistant pathogens.

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Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017

BMC Infectious Diseases ◽

10.1186/s12879-021-05996-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Cheng Lei ◽

Lisong Yang ◽

Cheong Tat Lou ◽

Fan Yang ◽

Kin Ian SiTou ◽

...

Keyword(s):

Respiratory Tract ◽

Lower Respiratory Tract ◽

Respiratory Tract Infections ◽

Pediatric Patients ◽

Respiratory Infections ◽

Upper Respiratory Tract ◽

Viral Etiology ◽

Upper Respiratory ◽

Syncytial Virus ◽

Tract Infections

Abstract Background Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao. Methods A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality. Results Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup. Conclusions This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.

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